Reduction of isatins

The synthesis of the right-hand fragment of ziprasidone started with a Wolff-Kishner reduction of isatin 43 to give the oxmdole 44 (Scheme 14). Friedel-Crafts acylation with chloroacetyl chloride afforded aryl ketone 45, which was reduced with triethylsilane in trifluoroacetic acid to the phenethyl chloride 46. The two fragments were joined by alkylation of 40 with 46 in the presence of Nal and Na2CO3 to give ziprasidone (4) in low yield. The yield of the coupling step was improved dramatically when the reaction was conducted in water (Scheme 15). 

Lithium aluminum hydride reduction of isatin gave mixtures of 3-hydroxyindolinc, indole, indigo, and indirubin with compositions depending upon the experimental conditions.246 The latter three products... 

An analytical procedure for organotin hydrides has been based on the reduction of isatin to oxindole.273... 

Reduction of isatin-3-oximes to the corresponding 3-aminooxindole has been carried out using stannous chloride in acetic acid51 or in hydrochloric acid.92 3-Aminooxindole has also been obtained by electrochemical reduction288 and catalytic hydrogenation.169 Reduction... 

The reduction of isatins with lithium aluminum hydride in pyridine gave indoles in moderate yields. However, the use of THF as a solvent under an inert atmosphere gave greater yields (86-92%) and this procedure was applied to the synthesis of substituted ellipticine... 

The products of partial reduction of isatin, dioxindole and oxindole, have been widely... 

Electrolytic reduction of isatin using a lead electrode and a saturated sodium carbonate solution as electrolyte gave dihydroxy-indole, whereas a mercury cathode and lead anode in neutral sodium sulfate gave hydroxyindole. Electrolytic reduction of 1-methylisatin using lead cathodes and 20% sulfuric acid gave 1-methyldihydroxy-indole a mercury cathode and neutral sodium sulfate gave 1-methyl-hydroxy indole. 

This compound is an inner anhydride of orthoarnidophenyl acetic acid, and is isomeric with indoxyl. It is formed by reduction of isatin with sodium amalgam [14], and of acetylorthoamidophenyl-glycollic acid with hydriodic acid [15]- It forms colourless needles, M.P. 120°, and exhibits simultaneously basic and acid properties. It reacts with nitrous acid, producing isatinoxime [24]. 

The formation of oxindol and dioxindol by reduction of isatin is, however, more in favour of the following constitution for these compounds —... 

When o-nitro-benzoylformic acid is reduced the amino compound formed loses water spontaneously and passes into isatin. Reduction of isatin chloride with zinc and acetic acid yields indigo. 

Reduction of isatins to afford oxindoles can be achieved by catalytic reduction in acid, or by the Wolff-Kischner process.3-Substituted indoles result from Grignard addition at the ketone carbonyl, followed by lithium aluminium hydride reduction of the residual amide, then dehydration. 

Although isatins having adjacent carbonyls of very different reactivity— amide vs. ketone—undergo a variety of chenucal reactions [86,87], the focus here is on synthetic transformations to indoles. Accordingly, isatins can be reduced directly to indoles (Scheme 11, equations 1-7) [16,89-93]. Given the availability of isatins from aromatic amines (e.g., Sandmeyer synthesis [86], Gassman synthesis [88]), the reduction of isatins to indoles can be an important alternative to other methods. 

C) for hours. Soriano (1993) reported a simple WoUf-Kishner reduction of isatin under mild condition. However, this method requires a 3-4 h time and the base, sodium ethoxide, should be freshly prepared, which presents a potential danger. It was observed that the reaction time was greatly decreased, when the reaction was carried out in household microwave oven. 

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